PROJECT SUMMARY There is a fundamental gap in the availability of cognitive outcome measures that are reliable and sensitive to detecting change among individuals with Down syndrome (DS) across the lifespan. Lack of such outcome measures represents an important problem to interpreting clinical trials aimed at improving the lives of individuals with DS. Without evidence-based cognitive outcome measures, future treatment trials in this population will remain suboptimal due to poor study measures. Despite some promising findings in currently recommended assessment measures/batteries, the evidence base for cognitive outcome measures in DS is limited. Multi-site studies evaluating the reliability and validity of outcome measures are the needed next step towards supporting the evaluation of new pharmaceutical and clinical interventions for individuals with DS across the lifespan. Working groups convened by NICHD of leading experts in DS led to recommendations of promising measures for use in this population. The current supplement proposes to extend the evaluation of psychometric properties of recommended promising measures of cognitive outcomes from childhood through to young adulthood. The overall objective of this supplement application is to establish the psychometric properties of individual clinical outcome measures in young adults with DS across the cognitive domains of executive functioning (inhibition, working memory, set-shifting), learning and memory, and processing speed. Our rationale for extending the age range is to expand the applicability of measures for use in clinical trials across a broader portion of the lifespan from childhood through to young adulthood, to describe the natural history of cognitive development during adulthood, as well as measure cognitive changes separate from the onset of dementia. We propose three specific aims: 1) To examine the psychometric properties of selected cognitive outcome measures with young adults with DS. 2) To evaluate differences in the psychometric properties of the measures as a function of variations in demographics and medical comorbidities. 3) To characterize the developmental trajectories of cognition and executive functioning. To achieve these aims, 100 adults ages 18-29 years with DS will participate in repeated neuropsychological assessments with follow-up evaluations at 2 weeks, 3 months, 6 months, and 1 year. Parents/Caregivers will complete ratings of executive functioning, adaptive behavior and behavioral concerns. Our parent grant research team is uniquely positioned to conduct this work, combining expertise in DS, neuropsychological assessment, medical conditions and measurement evaluation. We anticipate that this measurement study will provide critical guidance for future efficacy and effectiveness trials. Our goals are in line with the INCLUDE Project research priority to assemble a large study cohort, from ages 6-29 years, to characterize cognition and executive functioning across this portion of the lifespan. As our field continues to develop new pharmaceutical and clinical interventions, our project will support this work and have an impact on the 400,000 individuals with DS living in the United States.